PROJECT SUMMARY/ABSTRACT The recent opioid crisis across the United States has drawn national attention and resulted in the allocation of significant federal resources to substance use treatment and prevention efforts. American Indian (AI) communities, however, have faced a substance use crisis of similar scope for many years, without the benefit of proportionate attention and resources. Disparities in substance use disorder impacting AI populations are well-documented, and the roots of these disparities can be traced to significantly higher adolescent substance use among AIs compared to other ethnic groups in the U.S. AI youth report earlier initiation of substance use than their non AI peers. National trends of escalating opioid use are evident among AI populations as well, and appear, in fact, to be even more pronounced, reflecting the overall pattern of disparities observed across substances, with AI youth reporting greater heroin and OxyContin use than youth from other racial and ethnic groups. The imperative remains strong to direct attention and resources to focus on early prevention efforts for AI youth. In response to this need, researchers at the Centers for American Indian and Alaska Native Health in the Colorado School of Public Health at the University of Colorado have recently completed an intensive community-engaged process to rigorously adapt the Strengthening Families Program for Parents and Youth 10-14 for the cultural context of a Northern Plains AI community, creating a program optimized for AI families, Thiwhe Gluw?'akapi (TG, sacred home in which family is made strong). The current study will test the effectiveness of TG for delaying the onset of substance use among young adolescents. Based on evidence that the original Strengthening Families program may impact risk behaviors beyond substance use, and in response to requests from participating families and community partners to help address suicide risk among their youth, the current study will also test the impact of TG on suicidal ideation among youth. In addition, in recognition of the potential of for the TG program to have a reciprocal influence on the adults participating in the program with their children, capitalizing on parents' motivation to protect their youth and make concomitant positive changes in their own lives, the current study will examine effects on adult substance use as well. Examining effects on adult substance use is especially timely as the opioid epidemic rages in in this community, as around the country. In summary, this study will address three specific aims, testing effectiveness of the TG prevention program on three distinct sets of outcomes: (1) Substance use among youth: delaying the onset of use and reducing use among youth who initiated prior to program participation; (2) Suicide risk among youth: reducing suicidal ideation and other risk factors for suicide and increasing protective factors; and (3) Substance use among adults: Reducing use among adults participating in the program with their children who report problematic levels of use at program entry.